We intend to examine the genetic and/or epigenetic factors involved in the expression and suppression of the malignant phenotype in human cells. Analysis of the genetic factors involved will be accomplished by fusion of malignant cells with normal cells followed by assaying for malignancy in suitable immunosuppressed hosts. Detailed chromosomal analyses will identify the specific chromosome(s) involved in the expression and suppression of malignancy. The potential role of epigenetic factors will be studied by enucleating cells and fusing the enucleate cytoplasms with appropriate whole cells. Nuclear and cytoplasmic genetic markers are available, or will be generated, for selection of whole cell: whole cell, and whole cell: cytoplasm hybrid populations respectively. Characterizations of the hybrid cells produced will shed light upon the biologic properties of cells, e.g., cAMP content, agglutinability, etc., that truly distinguish malignant cells from non-malignant cells in vitro. The techniques to be developed in this study will also be useful for the general areas of somatic cell genetics, and cellular differentiation and development. BIBLIOGRAPHIC REFERENCES: E. J. Stanbridge. 1976. Cell fusion, genetic cartography, and malignancy. Lancet ii:525. E. J. Stanbridge and F. T. Perkins. 1977. Tumourigenicity testing in immunosuppressed mice: advantages and disadvantages. Joint WHO/IABS Symposium on Standardization of Cell Substrates for Virus Vaccines, Geneva, Switzerland, in press.